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[1]舒签汇,李 文,梅田恬,等.基于1,4-二氢吡啶衍生物抑制P-糖蛋白并增敏抗癌效应的研究[J].武汉工程大学学报,2025,47(05):480-486.[doi:10.19843/j.cnki.CN42-1779/TQ.202407029]
　SHU Qianhui,LI Wen,MEI Tiantian,et al.Inhibiting P-glycoprotein and sensitizing cancer cells to cisplatin using novel 1,4-dihydropyridine derivatives[J].Journal of Wuhan Institute of Technology,2025,47(05):480-486.[doi:10.19843/j.cnki.CN42-1779/TQ.202407029]
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基于1,4-二氢吡啶衍生物抑制P-糖蛋白并增敏抗癌效应的研究

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《武汉工程大学学报》[ISSN:1674-2869/CN:42-1779/TQ]

卷:
47
期数:
2025年05期
页码:
480-486
栏目:
现代大化工
出版日期:
2025-10-31

文章信息/Info

Title:
Inhibiting P-glycoprotein and sensitizing cancer cells to cisplatin using novel 1,4-dihydropyridine derivatives
文章编号:
1674 - 2869（2025）05 - 0480 - 07
作者:
湖北大学健康科学与工程学院，湖北 武汉 430062
Author(s):
School of Health Science and Engineering，Hubei University，Wuhan 430062， China
关键词:
Keywords:
分类号:
O626.13
DOI:
10.19843/j.cnki.CN42-1779/TQ.202407029
文献标志码:
A
摘要:
多药耐药性显著降低了化疗效果，并干扰肿瘤治疗进程，P-糖蛋白是ABC转运体家族中与肿瘤细胞多药耐药性密切相关的转运蛋白，其活性抑制可作为克服耐药性的潜在靶标；1,4-二氢吡啶类化合物具有广泛的药理学作用，也可作为P-糖蛋白抑制剂降低耐药性。制备多个1,4-二氢吡啶衍生物，即DHP-（1-6）(即为DHP-1，DHP-2，DHP-3，DHP-4，DHP-5，DHP-6)；以P-糖蛋白抑制剂维拉帕米为参照，分析DHP-（1-6)与P-糖蛋白的相互作用，获得潜在的结合位点与结合能信息。实验表明：顺铂耐药的肺癌细胞A549/DDP中，DHP-（1-6）都可能通过抑制P-糖蛋白活性阻滞罗丹明123的细胞外排；另一方面，通过顺铂与DHP-(1-6)的联合给药，发现所制备的1,4-二氢吡啶衍生物能有效提升耐药细胞对顺铂的敏感性，DHP-2能改善顺铂对A549/DDP细胞的抗肿瘤活性至IC50=13.12 μmol/L。开发的新型1,4-二氢吡啶衍生物具有良好的生物相容性，可有效抑制P-糖蛋白活性、显著降低癌细胞对顺铂的耐药性，有望用于抗肿瘤辅助药物的研发。
Abstract:
Chemotherapy is one of the common methods for treating malignant tumors. However, the multidrug resistance significantly reduces the efficiency of chemotherapy and interferes with tumor treatment. P-glycoprotein (P-gp), a transporter protein of the ABC transporter family, confers multidrug resistance (MDR) to cancer cells. Inhibiting its activity has emerged as a promising strategy to overcome chemoresistance. 1,4-dihydropyridine (DHP) compounds are known for their diverse pharmacological effects, including P-gp inhibition. In this study, a series of novel DHP derivatives (DHP-1 to DHP-6) was synthesized. Using verapamil, a classic P-gp inhibitor, as a reference, molecular interaction analyses revealed the potential binding sites and binding energies of these derivatives with P-gp. In cisplatin-resistant lung cancer A549/DDP cells, all DHPs (DHP-1 to DHP-6) inhibited P-gp-mediated efflux of rhodamine 123. Furthermore, co-administration of cisplatin with the DHP derivatives significantly sensitized the resistant cells to cisplatin. Notably, DHP-2 enhanced the antitumor activity of cisplatin, achieving an IC50 of 13.12 mmol/L against A549/DDP cells. The developed DHP derivatives exhibited good biocompatibility and potent P-gp inhibitory effects, effectively reversing cisplatin resistance. These findings suggest their promising potential as antitumor adjuvants.

参考文献/References:

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备注/Memo

备注/Memo:
收稿日期：2024-07-29
基金项目：小分子原料药精准制造湖北省重点实验室开放课题（KHLA01001）
作者简介：舒签汇，硕士研究生。Email：1912825889@qq.com
*通信作者：宋 蔚，博士，讲师。Email: songwei_83@hubu.edu.cn
王 凯，博士，教授。Email: kaiwang@hubu.edu.cn
引文格式：舒签汇，李文，梅田恬，等. 基于1,4-二氢吡啶衍生物抑制P-糖蛋白并增敏抗癌效应的研究［J］. 武汉工程大学学报，2025，47（5）：480-486.

更新日期/Last Update: 2025-11-03